MicroRNA-22-3p is associated with spinal cord injury regeneration and PTEN/STAT3 signaling

Spinal cord injury (SCI) is a debilitating condition with limited treatment options, where secondary injury mechanisms such as oxidative stress, cell death, and inflammation exacerbate tissue damage and impair recovery. MicroRNA-22 (miR-22) is recognized for its antioxidant, anti-inflammatory, and cell survival properties; however, its specific role in SCI remains unclear. This study aimed to investigate the effects of miR-22 modulation on neuronal survival and functional recovery in a rat model of SCI, with a particular focus on the PTEN/AKT and STAT3 signaling pathways. Following clip-compression induced SCI, rats were transfected with either a miR-22 mimic or an antagomir. Behavioral and electrophysiological assessments revealed that miR-22-overexpression improved motor recovery and proximal latency compared to the SCI-only and SCI + antagomir transfected groups. Histological analysis demonstrated enhanced neuronal survival in the miR-22 transfected group compared with the SCI and SCI + antagomir transfected groups. ELISA results showed reduced expression of the cell death markers Bcl-2 and Caspase-3. Furthermore, qRT-PCR analysis showed that miR-22 expression was downregulated following SCI and upregulated after miR-22 transfection. Elevated miR-22 levels were associated with reduced PTEN and STAT3 expression, partial restoration of CREB1 levels, while AKT mRNA expression remained unchanged. GFAP expression was increased after SCI but was not significantly affected by miR-22 treatment compared with the SCI group. Collectively, these findings suggest that miR-22 may be involved in neuroprotection and functional recovery following SCI and is associated with changes in PTEN- and STAT3-related signaling. Therefore, miR-22 may represent a potential therapeutic target for SCI, although further mechanistic and translational studies are required.